Effect of GIP and GLP-1 antagonists on insulin release in the rat.
Effect of GIP and GLP-1 antagonists on insulin release in the rat.
复制标题
GIP 和 GLP-1 拮抗剂对大鼠胰岛素释放的影响。
DOI：
10.1152/ajpendo.1999.276.6.e1049
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Wolfe,MM
中科院分区：
文献类型：
--
作者：
Tseng,CC;Zhang,XY;Wolfe,MM
葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽1（GLP-1）是从小肠释放的有效促胰岛素肽。为了检查它们对餐后胰岛素释放的相对贡献，在胃内葡萄糖餐后将特异性GIP拮抗剂（ANTGIP）和GLP-1拮抗剂exendin-（9-39）-NH 2输注到大鼠中。在对照组大鼠中，血浆葡萄糖和胰岛素水平在前20分钟内逐渐上升，然后下降。Exendin-（9-39）-NH 2给药在20分钟时抑制餐后胰岛素分泌32%，并伴随血糖浓度升高。相比之下，ANTGIP治疗不仅诱导胰岛素分泌减少54%，而且在葡萄糖餐后20分钟血浆葡萄糖水平降低15%。大鼠体内研究表明，ANTGIP显着抑制了小肠上部的葡萄糖摄入，这一效应可能是ANTGIP治疗大鼠中观察到的血糖水平下降的原因。当两种拮抗剂同时给予大鼠时，未检测到对胰岛素释放或血糖浓度的增强作用。葡萄糖餐刺激的GLP-1释放不受ANTGIP给药的影响，而在接受exendin-（9-39）-NH 2的大鼠中，餐后胰高血糖素水平降低。这些研究的结果表明，GIP和GLP-1在刺激胰腺胰岛素释放方面可能具有共同的机制。此外，GIP受体似乎在促进小肠中的葡萄糖摄取中起作用。
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are potent insulinotropic peptides released from the small intestine. To examine their relative contribution to postprandial insulin release, a specific GIP antagonist (ANTGIP) and a GLP-1 antagonist, exendin-(9—39)-NH2, were infused into rats after an intragastric glucose meal. In control rats, plasma glucose and insulin levels rose gradually during the first 20 min and then decreased. Exendin-(9—39)-NH2administration inhibited postprandial insulin secretion by 32% at 20 min and concomitantly increased plasma glucose concentrations. In contrast, ANTGIP treatment not only induced a 54% decrease in insulin secretion but also a 15% reduction in plasma glucose levels 20 min after the glucose meal. In vivo studies in rats demonstrated that glucose uptake in the upper small intestine was significantly inhibited by the ANTGIP, an effect that might account for the decrease in plasma glucose levels observed in ANTGIP-treated rats. When the two antagonists were administered to rats concomitantly, no potentiating effect on either insulin release or plasma glucose concentration was detected. Glucose meal-stimulated GLP-1 release was not affected by ANTGIP administration, whereas postprandial glucagon levels were diminished in rats receiving exendin-(9—39)-NH2. The results of these studies suggest that GIP and GLP-1 may share a common mechanism in stimulating pancreatic insulin release. Furthermore, the GIP receptor appears to play a role in facilitating glucose uptake in the small intestine.